To investigate the mechanism on photosensitive
dermatitis caused by
ketoprofen (KP) in humans, the following experiments were performed by topical application on guinea pigs. The
phototoxicity study involving treatment with 10%
solution of KP, its enantiomers (R-KP and S-KP),
loxoprofen, and
flurbiprofen revealed no phototoxic reactions. In the photoallergenicity study, KP and its enantiomers (0.5-2%
solution) induced skin reaction at all dosages; however,
loxoprofen and
flurbiprofen (1-5%
solution) did not induce such a photoallergenic reaction. These results suggest that the chemical structure of the
benzophenone chromophore in KP would be one of the important factors for induction of the
photoallergy since both
loxoprofen and
flurbiprofen do not possess this structure and hence lack photoallergenic potential. Furthermore, to assess time profiles of KP concentration in the skin and plasma, guinea pigs received a repeated topical application of R-KP and S-KP at a dosage of 40 mg/kg over a period of 3 days. Plasma KP concentrations were extremely low as compared to skin KP concentrations and were not detected at 72 h after the final dosing. At 24 h after the final dosing, KP concentrations in the skin with R-KP and S-KP treatment were 187.4 and 254.7 microg/g, respectively, and their half-lives were 80.5 and 84.4 h, respectively. KP concentrations at 336 h after final dosing were 11.3 microg/g for R-KP and 15.7 microg/g for S-KP treatment. The
acylglycerol-combined KP concentrations at 336 h were 2% or less as compared to KP concentrations with R-KP and S-KP treatment. There were no differences in KP concentrations in the skin between R-KP and S-KP and in combined KP concentrations between the enantiomers. The present study indicates that photosensitive
dermatitis after topical application of KP in humans, caused by photoallergenicity and not
phototoxicity, can be reproduced in the animal testing, and suggests that the skin reaction may be caused by the long period of retention of KP in the skin.